Estrogenism and Vulvovaginitis

Zearalenone has been detected in corn, oats, barley, wheat, and sorghum (both fresh and stored); in rations compounded for cattle and pigs; in corn ensiled at the green stage; and very rarely in hay. It has been detected occasionally in samples from pastures in temperate climates at levels believed sufficient to cause reproductive failure of grazing herbivores.

Clinical effects cannot be distinguished from excessive estrogen administration. Physical and behavioral signs of estrus are induced in young gilts by as little as 1 ppm dietary zearalenone. In pigs, zearalenone primarily affects weaned and prepubertal gilts, causing hyperemia and enlargement of the vulva (known as vulvovaginitis). There is hypertrophy of the mammary glands and uterus, and abdominal straining results in prolapse of the uterus in severe cases. Removal of affected grain results in return to normal in ~1 wk.

Zearalenone causes reproductive toxicosis in sexually mature sows by inhibiting secretion and release of follicle-stimulating hormone (FSH), resulting in arrest of preovulatory ovarian follicle maturation. Reproductive effects in sexually mature sows depend on time of consumption. Zearalenone fed at 3–10 ppm on days 12–14 of the estrous cycle in open gilts results in retention of corpora lutea and prolonged anestrus (pseudopregnancy) for up to 40–60 days. Zearalenone fed at ≥30 ppm in early gestation (7–10 days after breeding) may prevent implantation and cause early embryonic death. Zearalenone metabolites can be excreted in milk of exposed sows, resulting in hyperestrogenic effects in their nursing piglets.

In cattle, dietary concentrations >10 ppm may cause reproductive dysfunction in dairy heifers, although mature cows may tolerate up to 20 ppm.

Young males, both swine and cattle, may become infertile, with atrophy of the testes. However, mature boars appear unaffected by as much as 200 ppm dietary zearalenone.

Ewes may show reduced reproductive performance (reduced ovulation rates and numbers of fertilized ova, and markedly increased duration of estrus) and abortion or premature live births.

Diagnosis is based on reproductive performance in the herd or flock, clinical signs, history of diet-related occurrence, and excluding other known causes of infertility. Chemical analysis of suspect feed for zearalenone and careful examination of reproductive organs at necropsy are required. As a bioassay, virgin prepubertal mice fed diets or extracts of zearalenone-contaminated feed demonstrate enlarged uteri and vaginal cornification typical of estrogens.

Differential diagnoses include reproductive tract infections and other causes of impaired fertility such as diethylstilbestrol in the diet of housed stock. In grazing herbivores, especially sheep, the plant estrogens (eg, isoflavones associated with some varieties of subterranean and red clovers, and coumestans in certain fodders [eg, alfalfa]) should be considered.

Unless stock are severely or chronically affected, usually reproductive functions recover and signs regress 1–4 wk after intake of zearalenone stops. However, multiparous sows may remain anestrous up to 8–10 wk.

Management of swine with hyperestrogenism should include changing the grain immediately. Signs should stop within 1 wk. Animals should be treated symptomatically for vaginal or rectal prolapse and physical damage to external genitalia. For sexually mature sows with anestrus, one 10-mg dose of prostaglandin F_2α, or two 5-mg doses on successive days, has corrected anestrus caused by retained corpora. Alfalfa and alfalfa meal fed to swine at 25% of the ration may reduce absorption and increase fecal excretion of zearalenone, but this is often not considered practical. Feeding activated charcoal, cholestyramine, or alfalfa meal may reduce zearalenone absorption and retention, but the high concentrations needed generally render this impractical.